Project Summary - Abstract The UMass Mouse Metabolic Phenotyping Center (MMPC) involves a multidisciplinary group of investigators at UMass who perform an array of novel and sophisticated metabolic, analytical and functional experiments using state-of-the-art equipment for the purpose of investigating transgenic mice useful for understanding obesity, diabetes and its complications. The goal of the UMass MMPC is to provide comprehensive metabolic and functional characterization of transgenic mice using unique and standardized techniques mostly involving in vivo and physiological setting that are complemented by analytical experiments using serum/tissue samples and measure of islet and cardiovascular functions in mice. The UMass MMPC consists of 2 Phenotyping Cores. The Metabolism Core applies hyperinsulinemic-euglycemic clamp to assess insulin action and glucose metabolism in individual organs, hyperglycemic clamp to assess pancreatic ?-cell functions in conscious mice, metabolic cages to assess energy expenditure, activity and food intake, 1H-MRS to measure body composition, exercise studies using treadmill, and blinded drug trial studies. The Analytical and Functional Core consists of the complementary 3 sub-Cores. Analytical sub-Core uses Luminex and Cobas Chemistry Analyzer to provide a high-throughput and multiplexed measurement of serum/tissue levels of hormones, cytokines and metabolites, and performs molecular experiments to examine insulin/metabolic signaling. The Islet sub-Core performs elegant islet isolation and ex vivo and in vitro analysis of islet function and histology, and molecular analysis. The Cardiovascular sub-Core uses state-of-the-art Vevo2100 In Vivo Imaging System to conduct echocardiography and tissue Doppler imaging for cardiac structure and function analyses, telemetry to examine blood pressure and heart rates, standardized techniques to assess vascular and endothelial functions, and various elegant surgical models of cardiovascular diseases. Mice provided by the users are overseen by the Animal Core that processes the receiving, quarantine, and housing of mice. The Humanized Mouse Cell Transplantation and Assessment sub-Core will service the MMPC community by offering humanized mice and elegant technique to assess in vivo function of transplanted human islets and stem cell-derived ?-cells in immunodeficient mice. Lastly, administrative, financial and scientific operation, research & development program, and website & database are managed by the Administrative Core. Overall, the overarching goal of the UMass MMPC is to provide comprehensive characterization of mice using state-of-the-art equipment and elegant and standardized techniques as an important scientific resource to support the mission of the National MMPC consortium program.